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Observational Study
. 2015 May;15(5):1323-35.
doi: 10.1111/ajt.13107. Epub 2015 Mar 16.

Association between individual and combined SNPs in genes related to innate immunity and incidence of CMV infection in seropositive kidney transplant recipients

M Fernández-Ruiz  1 , I Corrales, M Arias, J M Campistol, E Giménez, J Crespo, M O López-Oliva, I Beneyto, P L Martín-Moreno, F Llamas-Fuente, A Gutiérrez, T García-Álvarez, R Guerra-Rodríguez, N Calvo, A Fernández-Rodríguez, J M Tabernero-Romo, M D Navarro, A Ramos-Verde, J M Aguado, D Navarro; OPERA Study Group
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Free article
Observational Study

Association between individual and combined SNPs in genes related to innate immunity and incidence of CMV infection in seropositive kidney transplant recipients

M Fernández-Ruiz et al. Am J Transplant. 2015 May.
Free article

Abstract

In this study, we assessed the association between single-nucleotide polymorphisms (SNPs) in seven candidate genes involved in orchestrating the immune response against cytomegalovirus (CMV) and the 12-month incidence of CMV infection in 315 CMV-seropositive kidney transplant (KT) recipients. Patients were managed either by antiviral prophylaxis or preemptive therapy. CMV infection occurred in 140 patients (44.4%), including 13 episodes of disease. After adjusting for various clinical covariates, patients harboring T-allele genotypes of interleukin-28B (IL28B) (rs12979860) SNP had lower incidence of CMV infection (adjusted hazard ratio [aHR]: 0.66; 95% confidence interval [CI]: 0.46-0.96; p-value = 0.029). In the analysis restricted to patients not receiving prophylaxis, carriers of the TT genotype of toll-like receptor 9 (TLR9) (rs5743836) SNP had lower incidence of infection (aHR: 0.61; 95% CI: 0.38-0.96; p-value = 0.035), whereas the GG genotype of dendritic cell-specific ICAM 3-grabbing nonintegrin (DC-SIGN) (rs735240) SNP exerted the opposite effect (aHR: 1.86; 95% CI: 1.18-2.94; p-value = 0.008). An independent association was found between the number of unfavorable SNP genotypes carried by the patient and the incidence of CMV infection. In conclusion, specific SNPs in IL28B, TLR9 and DC-SIGN genes may play a role in modulating the susceptibility to CMV infection in CMV-seropositive KT recipients.

Keywords: clinical research / practice; immune regulation; infection and infectious agents; infectious disease; kidney disease: infectious; kidney transplantation / nephrology; molecular biology: single polynucleotide polymorphism; translational research / science; viral: Cytomegalovirus (CMV).

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